Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer.
OBJECTIVE
The invasive growth of circulating tumor cells (CTCs) propagates cancer metastasis. The aims of this study were to evaluate the association of invasive CTCs, detected by a novel cell invasion assay, with disease stage, CA-125 level and patient survival.


METHODS
Peripheral blood samples from 71 patients undergoing evaluation for ovarian malignancy were assessed for the presence of invasive CTCs using a cell invasion assay that enriches and identifies tumor cells with a cell adhesion matrix (CAM). Invasive CTCs were identified as cells exhibiting CAM invasion (CAM+) and expressing standard epithelial markers (Epi+).


RESULTS
43 (60.6%) patients had detectable CTCs: 0/5 benign patients, 1/10 (10%) early stage, 39/52 (73.1%) late stage and 3/4 (75%) unstaged patients (p-value <0.001). CTC counts ranged from 0-149 CTCs/ml with stage III/IV patients exhibiting significantly higher mean counts (41.3 CTCs/ml) than stage I/II patients (6.0 CTCs/ml) and benign patients (0 CTCs/ml, p-value=0.001). A positive correlation between CTC count and CA-125 level was observed (Spearman correlation coefficient r=0.309, p-value=0.035). Kaplan-Meier curves revealed a significant decrease in disease-free survival in patients with detectable CTCs (median survival 15.0 months vs. 35.0 months, log-rank p-value=0.042). Tumor grade and tumor histology did not influence CTC detection.


CONCLUSIONS
Invasive CTCs can be detected in a majority of epithelial ovarian cancer patients and may predict shorter disease-free survival. Furthermore, higher CTC counts may reflect later stage disease and higher CA-125 levels.
Fan
Tina
T
Department of Medicine, Metastasis Research Laboratory, Stony Brook University, Stony Brook, NY 11794, USA.
Zhao
Qiang
Q
Chen
John J
JJ
Chen
Wen-Tien
WT
Pearl
Michael L
ML
D018394:CA-125 Antigen / Q000097:blood; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000097:blood / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate
D018394:CA-125 Antigen